Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

Abstract

Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

Acción de la estreptozotocina en un modelo experimental de inducción neonatal de la diabetes

“…Este fármaco provoca la destrucción selectiva de las células β de los islotes pancreáticos, única fuente de insulina en el organismo (1,3,6).…”

“…El momento, la dosis y la vía de administración resultan determinantes para el tipo de diabetes que se desee inducir. En la rata adulta la inoculación de diferentes dosis de este agente causa una deficiencia casi total de insulina y, por lo tanto, niveles elevados de hiperglucemia que simulan la diabetes de tipo 1 (1,3,7). Sin embargo, varios autores refieren que una única dosis elevada de estreptozotocina (100 mg/kg), administrada durante los primeros días de vida del conejo, provoca un déficit de insulina moderado y valores medios de hiperglucemia semejantes a los de la diabetes de tipo 2 en el transcurso de las siguientes semanas (1,2,6,8).…”

Extracellular HSP70 levels in diabetic environment in rats

“…2009; Dallaqua et al 2012;Damasceno et al 2014). In our diabetic model, after streptozotocin administration during neonatal period, the rats present hyperglycemia in first days of life due to necrosis of beta cells (Lenzen 2008).…”

Untitled

“…Streptozotocin is the most prominent diabetes inducing chemical entity used by many researchers due to its property of production of diabetes similar to human diabetes mellitus 15 . In the pancreatic cells, it produces free alkylating radicals by fragmenting the DNA molecule.…”